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- Title
Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder.
- Authors
Jian-Ye Liu; Yong-Hong Li; Huan-Xin Lin; Yi-Ji Liao; Shi-Juan Mai; Zhou-Wei Liu; Zhi-Ling Zhang; Li-Juan Jiang; Jia-Xing Zhang; Hsiang-Fu Kung; Yi-Xin Zeng; Fang-Jian Zhou; Dan Xie; Liu, Jian-Ye; Li, Yong-Hong; Lin, Huan-Xin; Liao, Yi-Ji; Mai, Shi-Juan; Liu, Zhou-Wei; Zhang, Zhi-Ling
- Abstract
<bold>Background: </bold>Yes-associated protein 1 (YAP 1), the nuclear effector of the Hippo pathway, is a key regulator of organ size and a candidate human oncogene in multiple tumors. However, the expression dynamics of YAP 1 in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance are unclear.<bold>Methods: </bold>In this study, the methods of quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC) were utilized to investigate mRNA/ protein expression of YAP 1 in UCBs. Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data.<bold>Results: </bold>Up-regulated expression of YAP 1 mRNA and protein was observed in the majority of UCBs by qRT-PCR and Western blotting, when compared with their paired normal bladder tissues. By IHC, positive expression of YAP 1 was examined in 113/213 (53.1%) of UCBs and in 6/86 (7.0%) of normal bladder specimens tissues. Positive expression of YAP 1 was correlated with poorer differentiation, higher T classification and higher N classification (P < 0.05). In univariate survival analysis, a significant association between positive expression of YAP 1 and shortened patients' survival was found (P < 0.001). In different subsets of UCB patients, YAP 1 expression was also a prognostic indicator in patients with grade 2 (P = 0.005) or grade 3 (P = 0.046) UCB, and in patients in pT1 (P = 0.013), pT2-4 (P = 0.002), pN- (P < 0.001) or pT2-4/pN- (P = 0.004) stage. Importantly, YAP 1 expression (P = 0.003) together with pT and pN status (P< 0.05) provided significant independent prognostic parameters in multivariate analysis.<bold>Conclusions: </bold>Our findings provide evidences that positive expression of YAP 1 in UCB may be important in the acquisition of an aggressive phenotype, and it is an independent biomarker for poor prognosis of patients with UCB.
- Subjects
ONCOGENES; TRANSITIONAL cell carcinoma; IMMUNOHISTOCHEMISTRY; MESSENGER RNA; POLYMERASE chain reaction; PROPORTIONAL hazards models
- Publication
BMC Cancer, 2013, Vol 13, Issue 1, p1
- ISSN
1471-2407
- Publication type
journal article
- DOI
10.1186/1471-2407-13-349